Pursuant to the notice published in the FEDERAL REGISTER of October 3, 1974 (39 FR 35697), stating that future memoranda of understanding between the Food and Drug Administration and others would be published in the FEDERAL REGISTER, the Commissioner of Food and Drugs issues the following notice:

The Center for Disease Control and the Food and Drug Administration have entered into an agreement concerning certain related objectives in carrying out their respective responsibilities. The agreement, which sets forth the working arrangements to be followed or adopted in respect to in vitro diagnostic product information exchange and scientific coordination, reads as follows:

I. Purpose. This agreement between the Center for Disease Control (CDC) and the Food and Drug Administration (FDA), both agencies of the Department of Health, Education, and Welfare (DHEW), Public Health Service, has been established to set forth procedures to foster information exchange and scientific coordination between the agencies in their respective programs for in vitro diagnostic products and licensed reagents, and to further delineate their individual responsibilities in the in vitro diagnostic product program.

II. Background. In vitro diagnostic products are defined in 21 CFR 328.3 as those reagents, instruments and systems intended for use in the diagnosis of disease or in the determination of the state of health in order to cure, mitigate, treat, or prevent disease or its sequelae. The definitions and other provisions of 21 CFR Part 328 relating to these products shall prevail in this agreement.

The FDA has the responsibility for the regulation of in vitro diagnostic products in interstate commerce under the provisions of the Federal Food, Drug, and Cosmetic Act. The FDA also has the responsibility of assuring the quality of in vitro diagnostic products purchased by the Veterans Administration, the Department of Defense and DHEW's Health Services Administration. Included are reagents of a biological origin that are used to test biological products licensed pursuant to section 351 of the Public Health Service Act (42 U.S.C. 263). The CDC is currently engaged in activities relating to the quality of such products in connection with its responsibility under the Clinical Laboratories Improvement Act of 1967 (CLIA) (42 U.S.C. 263a) and in administering a comprehensive national laboratory improvement program. Each agency has a responsibility to contribute to the total effort of the Federal Government in those areas in which it has recognized capability and experience.

III. Substance of Agreement

A. General: The responsibilities of each agency are further specified in this Memorandum of Understanding. However, it would be impractical to anticipate each task or need that may arise in a program of this magnitude, scope, and complexity. Also, the requirement for innovation in carrying out the in vitro diagnostic products program makes it necessary to amalgamate a wide variety of scientific, regulatory, and historical philosophies of each agency into the program with minimum duplication of effort.

As a general principle, the implementation of the provisions of this memorandum should not interfere with the programs of either agency. Should potential or real conflict develop, such matters will be further discussed and resolved through the interagency liaison representatives.

To further the necessary communication and coordination between the agencies, a designated representative from the CDC will be given sufficient advance notice for attending meetings of FDA advisory committees, classification panels, classification subcommittees, or other meetings that may reasonably be deemed to have a significant impact on the design or implementation of the program as it relates to the CDC. Similarly, the CDC will notify designated FDA representative of all meetings to which CDC is a party that impact on the development of information related to the overall regulatory program for in vitro diagnostic products. Information exchange between the CDC and FDA shall be accomplished (a) by information requests and responses as program needs dictate, and (b) by the development of a list of types of information to be approved by the interagency liaison representatives. Further aspects of the information exchange are dealt with in subsequent parts of this memorandum.

B. Compliance programs: FDA has the statutory authority to assure that all in vitro diagnostic products in interstate commerce comply with the provisions of the Federal Food, Drug, and Cosmetic Act, section 351 of the Public Health Service Act, and all applicable regulations. This includes statutory requirements and regulatory requirements in addition to the regulations in Part 328 (21 CFR 328). Additionally, consistent regulatory policy must be applied. Therefore, all questions regarding the compliance of a product with the act or regulations, including applicability, jurisdiction, labeling, or performance limits, shall be referred to FDA. CDC may provide information and consultation to the industry and user communities within CDC's field of competence and in matters concerning evaluations of the technical accuracy of labeling statements or omissions based on product development or evaluation work done by CDC and other areas to be identified by the interagency liaison representatives.

Both FDA and CDC have access to a considerable amount of information concerning product deficiencies in the areas of labeling and product performance. FDA shall forward to CDC a copy of each in vitro diagnostic product problem report that it receives. Additionally, FDA shall report to CDC each regulatory action that may result in inquiries to CDC (recalls, seizures, etc.), as well as periodically report all regulatory actions and significant voluntary industry corrections. CDC shall review and evaluate this information and provide FDA with any information in the possession of CDC that is related to the reports. This may include knowledge of individual products or batches, or knowledge based on its general experience with the product class or methodology. CDC, within the limits of its available resources, shall provide scientific review and evaluation to FDA regarding any such report when specifically requested to do so by FDA.

CDC has access to information regarding product labeling and performance through sources such as its product evaluation programs, proficiency testing programs related to its responsibilities under the CLIA, and epidemiology surveillance programs. Results of CDC's evaluation studies of marketed in vitro diagnostic products are reported in published scientific articles or as informational items. These reports are provided to the manufacturers of evaluated products, to consumers, and to the FDA.

CDC reports directly to the manufacturer, whether or not a particular lot or batch of reagent voluntarily submitted for evaluation meets published performance specifications. A compilation, listed by manufacturer, of the lots found to meet performance specifications is distributed on a monthly basis. FDA will be advised of the companies participating in the voluntary program and of those lots meeting performance specifications. Information on any lot of product evaluated by CDC will be available to FDA upon request.

CDC shall immediately report to FDA those problems that clearly represent a potential health hazard. For any such reports or summaries, CDC may, at its discretion, provide an evaluation and recommendation.

On request of FDA, in those areas in which CDC has scientific expertise and adequate resources, CDC will perform such product evaluation as necessary to support FDA regulatory responsibilities. This will include, where necessary, the proper protection, accountability, and handling of Official and Investigational Samples, selection or development of appropriate testing protocols, the acquisition of appropriate specimens, the testing of products, and preparation of a final report in a format suitable for use by FDA in a regulatory action.

C. Development of product class standards: The FDA, based on the recommendations of its advisory committee panels, will categorize and classify products for the purpose of effective regulation.

The FDA, in conjunction with its advisory committee, will propose priorities for the development of Product Class Standards and define the scope of such standards or criteria for scientific review.

In recognition of its scientific knowledge and experience, CDC will advise FDA on the feasibility of developing a particular product class standard, help identify those characteristics of the products within the class that should be addressed, participate in the development of the scientific basis for the product class standard, and consult in the development of time schedules for such activities.

The scientific basis for a product class standard includes such elements as reference, calibrator, and control materials; reference methods; appropriate specifications and performance requirements relative to the clinical usefulness of results; and procedures and materials for evaluating products.

Whenever, and to the extent that CDC states that its resources or interests preclude the timely development of the basis for a particular product class standard, the FDA may elect to assign this particular responsibility to another organization or agency, or to use its own resources.

FDA has the responsibility for the coordination, development, promulgation, and enforcement of product class standards established in accordance with 21 CFR Part 328. Three procedures for developing product class standards are provided in 21 CFR Part 328: (1) An existing standard may be utilized, (2) interested persons outside FDA may develop a proposed standard, or (3) FDA may develop the standard.

FDA will consult with CDC primarily before deciding which of the three procedures will be pursued.

D. Confidentiality and release of information: The nature and importance of the in vitro diagnostic products program are such that scientific, technical, and medical information, data, and opinion must be obtained early in the consideration of the development of a product class standard from a wide spectrum of qualified persons and organizations.

The CDC may share materials relating to the scientific basis for a product class standard with any appropriate party. Any such material or documents shall be clearly marked on each page to prevent any misunderstanding of its nature, i.e., it is not a draft product class standard. Such information, other than trade secret or confidential information, that would otherwise be exempt from disclosure under the Freedom of Information Act, must be available to any interested party if it has been shared by CDC with any person other than a regular or special government employee. The CDC will advise FDA of the exposure and distribution of each such document.

The FDA will provide to CDC any records and documents necessary for the efficient furtherance of this program. Documents that may be exempt from public disclosure in accordance with the provisions of the Freedom of Information Act and 21 CFR Part 4 shall be identified as such by FDA and protected as confidential by CDC. Any requests for disclosure of such documents received by CDC from the public will be referred to FDA. Parts 2 and 4 (21 CFR Parts 2 and 4) govern the release of documents, drafts of regulations, and the publication of proposed and final orders in the FEDERAL REGISTER. The FDA will share with CDC such draft regulations; these drafts may not be disclosed to, or discussed with, the public until publication for comment in the FEDERAL REGISTER.

E. Interagency liaison: Interagency liaison representatives shall consist of one representative and one alternate from each agency. The representatives shall consider long term policy and planning for the total program in relation to the resources and responsibilities of each agency. Additionally, they shall be the principal focus for interagency problems that cannot be resolved at lower levels. The representatives shall act as a focal point for the stimulation and coordination of information dissemination to each agency on matters of mutual interest. The representatives shall also be responsible for ensuring that items of particular interest or concern are placed on the agenda for deliberation. A minimum of two meetings will be held each year, with prior agreement on the agenda. The representatives will be free to include, as participants at meetings, personnel from their own agency, depending upon the agenda items, with prior agreement by both agencies. Reports in the form of minutes of interagency liaison representatives' deliberations shall be prepared and submitted to each agency for circulation and review in order to ensure adequate information dissemination. In addition, the interagency liaison representatives shall, on a fiscal year basis, prepare and submit to both agencies a formal plan that identifies the specific activities of both agencies related to the development of product class standards. This plan should be prepared and submitted to the parent agencies at least 3 months prior to the initiation of the target fiscal year. The plan shall identify the FDA priorities for the development of product class standards during the forthcoming fiscal year, and the involvement of CDC, including input, review, and evaluation requirements. In addition, the plan shall include the priorities for the development of the scientific basis for standards, with CDC plans for accomplishments during the target fiscal year. The submission of the plan should also identify those areas in which FDA has indicated a high-priority need for the development of a scientific basis for a product class standard and where CDC, due to resource limitations or other reasons, is not able to respond to the FDA requirement. The formal plan shall only consider and identify activities of both agencies pertaining to the development and promulgation of in vitro diagnostic product class standards. Other related activities of mutual interest and participation will be considered on an ad hoc basis.

VI. Period of Agreement. This agreement, when accepted by both parties, will be effective from date of signature through and indefinite period and may be modified or terminated by mutual consent of both parties upon 120 days advance written notice to the other.

Effective date. This Memorandum of Understanding became effective December 31, 1975.

Dated: January 15, 1976

Approved and Acceptedfor the Center for Disease ControlSigned by: David J. Sencer, M.D., DirectorCenter for Disease ControlDate: December 31, 1975

Approved and Acceptedfor the Food and Drug AdministrationSigned by: Alexander M. Schmidt, M.D.Commissioner of Food and DrugsDate: December 18, 1975